Parasite Immunology最新文献

Osteoarthritis (OA), a degenerative condition, severely impacts the quality of life in elderly individuals. Current clinical treatment options for OA remain limited. The polarisation of synovial macrophages plays a pivotal role in OA progression. SJMHE1, a peptide derived from Schistosoma japonicum (S. japonicum), has demonstrated the ability to inhibit inflammatory responses such as those seen in asthma and enteritis. Herein, SJMHE1 was administered via intra-articular injection to rats with anterior cruciate ligament transection (ACLT)-induced OA. Its effects on synovial inflammation, cartilage degradation and macrophage polarisation were assessed. Additionally, SJMHE1-stimulated macrophages were co-cultured with chondrocytes to examine chondrocyte degradation and apoptosis. The effect of the peptide on the expression of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) derived from patients with OA was also evaluated. SJMHE1 treatment delayed OA progression in elderly rats. It inhibited M1 macrophage polarisation, promoted M2 macrophage polarisation, reduced synovial inflammation and alleviated cartilage degradation. In the synovium, SJMHE1 downregulated proinflammatory cytokine IL-6 and upregulated the anti-inflammatory cytokine IL-10. In vitro, SJMHE1-treated macrophages preserved chondrogenic properties and inhibited chondrocyte apoptosis. Furthermore, SJMHE1 suppressed inflammatory cytokine production in PBMCs from patients with OA. The results suggest that SJMHE1 could represent a potential therapeutic approach for managing OA.

The severity of malaria is associated with low antioxidant availability and elevated free radical production, which induces oxidative damage in cerebral and pulmonary microcirculation. This can be mitigated by dietary antioxidants. We investigated the protective effects of lycopene (LYC) against oxidative changes induced by Plasmodium berghei (Pb). Mice were infected by intraperitoneal injection of 10⁶ parasitized red blood cells and treated orally with LYC (3.11 mg/kg bw/day) or N-acetylcysteine (NAC, 62 mg/kg bw/day). Evaluations were conducted at 1-, 4-, 8- and 12-days post-infection. We measured thiobarbituric acid reactive substances (TBARS), antioxidant capacity by ABTS (AC-ABTS) and DPPH (AC-DPPH) inhibition, uric acid (UA) and nitric oxide (NO) in brain and lung tissues. Infection led to elevated TBARS, AC-ABTS, AC-DPPH, UA and NO, resulting in animal mortality. LYC significantly attenuated the infection-induced increases in TBARS, UA and NO levels compared to Pb (p < 0.0001) and NAC + Pb groups (p < 0.0001) normalising them to Sham levels. These findings highlight LYC's therapeutic potential against malaria-related oxidative stress.

Kala-azar, or visceral leishmaniasis (VL), is a parasitic disease caused by Leishmania spp., characterised by fever, weight loss, splenomegaly, hepatomegaly, and anaemia. This study evaluated the relationship between hepcidin, inflammation, iron metabolism, and hypersplenism in VL-associated anaemia. In this cross-sectional study, confirmed VL patients without recent transfusions were assessed. Haematological and inflammatory parameters were analysed using correlation and multivariate regression tests. Anaemia was present in 95.2% of the sample, predominantly normocytic (59.5%) and normochromic (76.2%), or microcytic (40.5%) and hypochromic (23.8%). Inflammatory markers were markedly elevated in most patients, particularly hepcidin, which was increased in 97.6% of cases (median: 351.46 ng/mL), suggesting persistent inflammation and impaired iron bioavailability. However, IL-6, CRP, and ferritin showed weak to moderate negative correlations with hepcidin (ρ = -0.33, ρ = -0.66, and ρ = -0.30, respectively). These findings highlight the complex interplay between anaemia and inflammation in kala-azar, with elevated hepcidin levels and paradoxical correlations with inflammatory markers. They underscore the central role of splenomegaly in VL-related anaemia and suggest potential contributions from other factors affecting iron metabolism, such as erythropoietin and erythroferrone. Understanding the dynamics of these markers throughout disease progression and treatment may further elucidate the pathophysiology of VL and support the development of targeted therapies.

Demodex mites are commensal ectoparasites in human pilosebaceous units that become pathogenic at high levels, causing demodicosis, which may be primary or secondary to immunosuppression. Thyroid hormones, with skin receptors, impact immune functions and epidermal inflammation. We hypothesised that skin features like xerosis and papular lesions, common in demodicosis, may also appear in autoimmune thyroid diseases, with immune dysregulation increasing Demodex colonisation. We recruited 201 patients with demodicosis or rosacea at Kayseri City Education and Research Hospital. Thyroid hormones (TSH, T3, and T4), anti-TPO antibodies, and demodex count measured by Standard Superficial Skin Biopsy were assessed. Patients were classified as Type 1 (erythema, telangiectasia, and rough skin) or Type 2 (papules and pustules) demodicosis. Results revealed that patients with elevated anti-TPO levels had significantly higher demodex counts (p < 0.05). Demodex positivity and anti-TPO levels were strongly associated with Type 2 demodicosis (p < 0.001, p = 0.008). There was a positive correlation between demodex count and anti-TPO (r = 0.144, p = 0.043), with a predictive value for anti-TPO positivity (p = 0.004). Our findings suggest that increased demodex counts in Type 2 demodicosis correlate with autoimmune thyroid disease risk, highlighting the potential of combined Demodex count and thyroid antibody assessments for early diagnosis.

The interest in nanotechnology applications in medicine, particularly for combating microbial infections, has surged in recent years. This study investigated the in vitro and in vivo antileishmanial effects of copper nanoparticles (CuNPs) that were green synthesised using Capparis spinosa fruit extract, both on their own and in conjunction with paromomycin (PM). CuNPs were synthesised from a methanolic extract of C. spinosa. We assessed the in vitro antileishmanial activity of CuNPs (10-200 μg/mL) as well as the same concentrations of CuNPs (10-200 μg/mL) combined with PM (10-200 μg/mL), targeting the promastigote and amastigote forms of Leishmania major. Additionally, we evaluated the cytotoxic effects of CuNPs on THP1 cells. Subsequently, we tested these formulations on female BALB/c mice infected with L. major. The study measured footpad swelling, quantified parasite load through real-time PCR, and assessed levels of cytokines such as interleukin-4 (IL-4) and gamma interferon (IFN-ɤ), nitric oxide (NO), and arginase (ARG). The results demonstrated that CuNPs, particularly when combined with PM, significantly inhibited (p < 0.001) the growth of L. major promastigotes and amastigotes and stimulated IFN-ɤ, NO production and reduced IL-4 and ARG levels (p < 0.05). Importantly, CuNPs exhibited minimal cytotoxicity towards THP1 cells. In infected mice, the treatment with CuNPs, notably in combination with PM, resulted in a significant (p < 0.05) reduction in the mean number of parasites. Treatment with CuNPs at concentrations of 100 and 200 mg/mL led to a decrease in lesion diameter. The results of this study highlight the potent antileishmanial activity and synergistic effects of CuNPs, both alone and in combination with PM, against L. major promastigotes and amastigote forms, as well as their potential in treating cutaneous leishmaniasis (CL) in BALB/c mice.

The nematode Dictyocaulus viviparus causes parasitic bronchitis in cattle. There is a vaccine based on irradiated larvae against this parasite. However, no memory response is induced, and donor calves are needed for culturing the larvae. Therefore, a well-defined subunit vaccine would be welcomed. Because thrombospondin-like protein (TLP) is an immunodominant protein from the brush border of adult parasites, it was tested as a vaccine candidate. Calves (n = 7) were vaccinated twice with TLP in Quil-A, and antibody responses, IgG2 allotypes and protection were determined. Protection is defined here as decreased worm counts from challenge infection compared with age-matched control calves (N = 7). Only 27% protection (not significant) was found in the vaccinated calves. However, strong IgG and IgE booster responses occurred after challenge infection, mostly directed against the glycan-phosphorylcholine moiety of the protein. Most interesting was the difference in protection in calves of the different IgG2 allotypes. The two best protected calves from the vaccinated group were the only two calves of the homozygote IgG2^b genotype. Because the IgG2^b has a more rigid hinge region than the IgG2^a allotype, it is more resistant to parasite proteases or parasite Ig binding proteins, and it is a better complement activator. Therefore, even with the small number of calves from this study, results suggest calves of the homozygous IgG2^b genotype might be better protected against D. viviparus than calves of other genotypes.

Around 90% of those at risk for schistosomiasis live in Africa, with urogenital schistosomiasis (UGS) prevalent in Sub-Saharan Africa. This study examines Schistosoma mansoni egg and worm antigens as cost-effective diagnostic alternatives, addressing challenges in maintaining S. haematobium in animal models. Sera and urine samples from schistosomiasis endemic and non-endemic areas were analysed against S. mansoni worm (Sm SWA) and egg antigens (Sm SEA) using indirect ELISA to detect S. haematobium specific antibodies. Microscopy was adopted as the diagnostic reference standard. Sensitivity (SS) ranged from 80% to 96%, and specificity (SP) ranged from 42% to 90%. Sm SWA showed slightly higher sensitivity than Sm SEA in negative non-endemic (NNE) populations. The best area under the curve (AUC) was 0.96 for Sm SEA-NNE. Both antigens performed better in diagnosing UGS in non-endemic samples, suggesting their suitability among travellers arriving from endemic areas. The anti-schistosomal IgG responses to Sm SWA and SEA in both negative endemic (NE) and NNE samples were statistically significant (p < 0.0001) compared to positive samples, except in NE sera samples tested with Sm SEA. Key findings indicate that Sm SEA and SWAP are effective diagnostic tools for S. haematobium infection, with high sensitivity suggesting their potential for new immunodiagnostic methods for UGS.

Mir-10a acts in signalling pathways regulating transcription, translation, and RNA-mediated gene silencing, while IFNG acts in the T-cell receptor signalling pathway. Thus, both can be considered potential targets for understanding regulatory processes in chronic inflammation in patients with schistosomiasis. Populations in endemic areas receive mass and indiscriminate praziquantel treatment, and yet patients often have a history of multiple infections. To investigate the regulatory and prognostic capacity of miR-10 and IFNG in patient immunity, we evaluated the expression of miR-10a and IFNG as biomarkers of inflammation and their correlation with praziquantel treatment. miR-10a did not present evidence as a biomarker of inflammation in the therapeutic follow-up in schistosomiasis. However, the levels of IFNG expression were significantly higher before treatment.

Frequent recrudescence is responsible for persistent Plasmodium infection after the acute stage. Our previous study demonstrated that phagocytic cells are essential for controlling Plasmodium chabaudi chabaudi AS (P. chabaudi) recrudescence. Nevertheless, the specific type of phagocytic cells involved in controlling P. chabaudi recrudescence, as well as their underlying molecular mechanisms of action, remain elusive. Herein we employ single-cell RNA sequencing (scRNA-seq) to analyse splenic phagocytic cells during both the acute and recrudescent phases of P. chabaudi infection. Using scRNA-seq, we found that monocyte-derived macrophages (MDMs) declined during the acute stage of P. chabaudi blood-stage infection, and then expanded rapidly in the recrudescence stage. The changing trend of MDMs was confirmed by flow cytometry. To explore the potential role of MDMs in controlling parasitemic recrudescence, MDMs were reduced by a low dose of clodronate liposomes (CLs) during the recrudescence stage, which significantly elevated the P. chabaudi parasitemia. Additionally, no significant difference in the proportion of splenic MDMs or classical monocytes (CMs) within the monocyte population was observed between the infected CCR2^-/- mice and their control littermates, suggesting that the transition from CMs to MDMs may not occur in this model. The results indicate that MDMs potentially play a protective role in preventing malarial parasitemic recrudescence, offering valuable insights into immune-based interventions against Plasmodium infection and potentially contributing to the prevention of malaria transmission.

Cryptosporidiosis is an important enteric disease, causing diarrhoea and malabsorption similar to Rotavirus and targeting young children and immunocompromised individuals, especially AIDS patients. However, there is a lack of fully effective drugs and vaccines against it. This study was done with the aim of investigating the anti-parasitic and anti-inflammatory effects of omeprazole versus nitazoxanide and their combination on Cryptosporidium parvum (C. parvum) infection in immunosuppressed experimental mice. To achieve this aim, histopathological analysis, scanning electron microscopy (SEM), estimation of oocyst shedding and measurement of tumour necrosis factor alpha (TNF-α) levels in sera of mice and the optical density of inducible nitric oxide synthase (iNOS) immunoreactivity in intestinal tissues were performed. Regarding the results, oocyst shedding showed an obvious reduction with omeprazole more than nitazoxanide. Similar results were detected on both histopathological examination (by haematoxylin and eosin and periodic acid-Schiff stains) and SEM with marked improvement in pathology detected in the combination therapy treated group. TNF-α showed reduced levels in the sera of all treated groups indicating a reduction of immunopathology with treatment. Also, the cytoplasmic expression of iNOS in the intestinal epithelium of mice was markedly reduced in all treated groups indicating a reduction of oxidative stress. From these results, omeprazole was found to be superior to nitazoxanide in treating cryptosporidiosis and the use of the two drugs as a combined therapy showed the best results.